A Novel Therapeutic Target for Radiation-Induced Hematological Malignancies: Calcium Calmodulin Kinase Kinase 2
Abstract
This proposal examines the Fiscal Year 2014 Peer Reviewed Cancer Research Program Topic Areas of (1) blood cancers and (2) cancers related to radiation exposure including occupational and environmental exposure and modulation by host factors. Furthermore, the proposed study addresses the Military Relevance Focus Areas of gaps in cancer treatment that may affect the general population but have a particularly profound impact on military health. The scientific objective of this proposal is to establish that a protein called calcium/calmodul-independent kinase kinase 2 (CaMKK2) can be a new treatment target for blood cancers associated with the exposure to ionizing radiation. The reason for this study is based on our previous findings that CaMKK2 is found in specific types of blood cells and that its loss changes blood cell function and inflammation. More recently, we have found that loss of CaMKK2 stops the development of cells that can help the tumor grow. Therefore, we have begun to explore CaMKK2 as a target in blood cancers and have made the significant findings that mice without CaMKK2 do not develop two types of blood cancer. We suggest that this protein, CaMKK2, plays a central role in tumor growth. More specifically, we will test whether the inhibition of CaMKK2 within specific blood cell types will increase the immune response and stop tumor progression. The proposed study will be applicable to patients with blood cancers by improving our understanding of how the immune system contributes to blood cancer growth and elimination. We will increase our understanding of how to alter the immune system by studying cells that we can deliver to patients to fight cancer. Patients with blood cancers will benefit from this research because we will develop new approaches to treating cancer. Furthermore, we are testing drugs that can improve the way our body kills cancer cells. Our results will be useful to all patients with blood cancer, and the findings may also help patients with solid tumors in the future. Although this study involves basic cancer research, we believe the findings from our work could be used to treat patients with blood cancer within a few years. We are also studying drugs that can reduce the growth of blood cancer cells in patients with existing cancer. The proposed research is relevant to active duty Service members and other military beneficiaries because we will investigate how radiation affects blood cancer development and treatment by testing new ideas involving immune function. Military personnel may encounter radiation during service and this study will improve the treatment of cancer related to radiation. Finally, these research areas are important to anyone that has been exposed to radiation or that has blood cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510443
Entities
People
- Nelson J Chao
Organizations
- Duke University
- United States Army